A multiparametric approach is being utilized to study the interaction of Trypanosoma cruzi with vertebrate cells. Vertebrate cell X T. cruzi hybrids have been produced which are stable and express parasite antigens. Changes in the intracellular cycle of T. cruzi have been quantified as well as the effects of immune human chagasic serum on the ability of the parasite to interact with human cells. The interference in penetration of vertebrate cells by T. cruzi trypomastigotes has been demonstrated using enzyme inhibitors. Reactivation of virulence has been achieved in the Ernestina strain of T. cruzi via a natural route following 14 years of continuous in vitro culture.